This invention broadly relates to treatment strategies for arthritis. More specifically, the invention relates to prophylactic, ameliorative and curative drug therapies for arthritis.
Arthritis is a collective term for number of different conditions that cause pain, swelling and limited movement in joints and connective tissue throughout the body. Specific causes for arthritis are not yet known for most forms of the disease. The condition is usually chronic. The main symptoms of arthritis are joint pain, joint stiffness or inability to move a joint normally, and sometimes swelling that lasts more than two weeks. Most treatment programs include a combination of medication, exercise, rest, use of heat and cold, joint protection techniques, and sometimes surgery.
The three most prevalent forms of arthritis are osteoarthritis (OA), fibromyalgia (FM), and rheumatoid arthritis (RA).
Osteoarthritis (OA) is a degenerative joint disease characterized by a breakdown of the joint""s cartilage. Cartilage functions to cushion the ends of the bones at each joint. A breakdown of the cartilage causes the bones to rub against each other, causing pain and loss of movement. OA primarily affects hands and weight-bearing joints, such as the knee, hips, feet and back. Risk factors for OA include advanced age, obesity, joint injury, and genetic disposition. Suggested causes for OA include an abnormal release of destructive enzymes from the cartilage cells themselves, and inherent defects in the way joints fit together. Most people over 60 suffer from OA, but only about one-third of those over 60 exhibit symptoms of OA.
Conventional treatment of OA focuses on decreasing pain and improving joint movement. Medications include aspirin, acetaminophen, ibuprofen and nonsteroidal anti-inflammatory drugs (herein after NSAIDs) for pain relief and inflammation reduction. Corticosteriod injection directly into affected joints in acute cases is also employed. Other noninvasive techniques commonly used to control OA include heat/cold treatment, exercise, joint protection and weight control.
Fibromyalgia (FM) is manifest as widespread pain affecting muscles and attachments to the bone. The patient may also exhibit tender points, specific areas that hurt when pressure is applied. Other symptoms can include fatigue, sleep disturbances, migraine headaches, irritated bowel syndrome, chest pain and nervous system symptoms such as depression.
Conventional treatment of FM include use of medications including aspirin, acetaminophen, ibuprofen or NSAIDs for pain relief and inflammation reduction.
Rheumatoid arthritis (RA) is an inflammatory disease having many components, including an autoimmune disorder aspect. The autoimmune disorder aspect is generally characterized by inflation of the membrane lining the joint resulting from an attack upon the joint by the body""s own immune system. The inflammation cause pain, stiffness, warmth, redness and swelling. The inflamed joint lining, call the synovium, can invade and damage surrounding bone and cartilage. The involved joint can lose shape and alignment, resulting in pain, loss of movement and possible destruction of the joint. Early in the disease, people may notice general fatigue, soreness, stiffness and aching. Pain usually occurs in the same joints on both sides of the body and will usually start in the hands or feet. RA can also affect wrists, elbows, shoulders, neck, knees, hips and ankles. Other symptoms include lumps, called rheumatoid nodules, under the skin in areas subjected to pressure, such as the back of elbows.
RA can be diagnosed by a laboratory test for rheumatoid factor, an abnormal substance found in the blood of about 80% of adults with RA However the presence or absence of rheumatoid factor does not in itself indicate that one has RA. An overall pattern of symptoms, medical history and physical examination are also used in diagnosing RA.
Conventional treatment of RA focuses on reducing swelling, relieving pain and stiffness, and maintaining normal joint function. Medications include NSAIDs for controlling inflammation, joint pain, stiffness and swelling. Disease-modifying drugs include low doses of prednisone, methotrexate, hydroxychloroquine, azulfidine, gold salt and cyclosporin, used alone or in combination. Some combination of exercise, rest, medication, joint protection, physical and occupation therapy, and surgery is also used to treat RA patients.
RA is characterized by striking age-sex disparities. The incidence of RA in women increases steadily from the age of menarche to its maximal incidence around menopause. The disease is uncommon in men under age 45, but its incidence increases rapidly in older men and eventually approaches the incidence in women. These observations strongly suggest that androgens may play some role in RA. Dehydroepiandrosterone (DHEA), an adrenal product, is the major androgen precursor in men and women. Its production is dependent upon age, zig in the 2nd and 3rd decades in women. DHEA levels are low in both men and women with RA, and recent data show that levels of this hormone may be depressed before onset of the disease. The menopausal peak of RA onset suggests estrogen and/or progesterone deficiency may also play a role in the disease. RA typically remits during pregnancy, in parallel with increasing levels of corticosteroids, estrogens and progesterone. Oral contraceptives, which generate a condition of pseudopregnancy, also decrease the risk of RA. These data argue that adrenal and gonadal steroid hormones affect the development of RA. In addition, several studies indicate that corticosteroid production is inappropriately low in patients with RA.
Traditional treatment regimens for arthritis, including medications for reducing tissue inflammation, often meet with limited success. Hence, the search continues for alternative treatments for arthritis patients.
The invention is directed to the prophylactic, ameliorative and curative treatment of arthritis by administering xcex945-androstene-3xcex2-ol-7,17-dione and precursors thereof which are readily metabolized in vivo to xcex945-androstene-3xcex2-ol-7,17-dione but essentially incapable of being metabolized to androgens, estrogens or dehydroepiandrosterone.